Mapping the rat somatosensory pathway from the anterior cruciate ligament nerve endings to the cerebrum

The anterior cruciate ligament (ACL) serves as the primary restraint to anterior tibial translation. In addition to this biomechanical function, the ACL appears to have a function in neuromuscular control. This hypothesis was formulated after the discovery of mechanoreceptors within the ACL. The full somatosensory pathway from the ACL to the cerebrum has yet to be elucidated. In order to map this sensory pathway, we conducted a viral trans-synaptic tracing experiment using the neurotropic pseudorabies virus (PRV). The pseudorabies virus was injected into the ACL of rats and allowed to replicate and spread trans-synaptically for 6-7 days. The brain and spinal cord of each sacrificed rat was then removed and processed immunohistochemically to detect the presence of PRV. PRV-immunoreactive neurons were found to be localized in several different regions from the spinal cord to the cerebrum. Four nuclei in the reticular formation of the brain stem demonstrated strong positive labeling: the mesencephalic reticular nucleus, magnocellular reticular nucleus, paragigantocellular reticular nucleus, and gigantocellular reticular nucleus. This finding suggests that the nerve endings of the rat ACL project into the cerebrum and that the reticular formation may play an important role in the afferent pathway of those nerve endings.     

A methoxylated fatty acid isolated from the brown seaweed Ishige okamurae inhibits bacterial phospholipase A2

A methoxylated fatty acid that inhibits phospholipase A(2) (PLA(2); EC 3.1.1.4) was purified from the brown seaweed Ishige okamurae. Approximately 8.1 mg of the inhibitory compound, 7-methoxy-9-methylhexadeca-4,8-dienoic acid, was isolated from 1 kg of I. okamurae powder. Recombinant PLA(2) derived from the pathogenic bacterium Vibrio mimicus was used as the target enzyme. The methoxylated fatty acid compound competitively inhibited PLA(2) with a Ki value of 3.9 microg/mL. The concentrations required for 50% inhibition of PLA(2), oedema and erythema were 1.0 microg/mL, 3.6 mg/mL and 4.6 mg/mL, respectively. The compound strongly inhibited PLA(2) activity in vitro and had potent antiinflammatory activity in vivo.     

Comparison of functional results with navigation-assisted minimally invasive and conventional techniques in bilateral total knee arthroplasty.

This study was undertaken to compare the clinical and radiological results achieved using navigation-assisted minimally invasive surgery (NA-MIS) and conventional (CON) techniques in 42 bilateral total knee arthroplasty (TKA) patients with a minimum follow-up of one year. Clinical evaluations were performed using range of motion (ROM), Hospital for Special Surgery (HSS) scores, and Western Ontario and McMaster University (WOMAC) scores (pain, functional, and total) at 3, 6 and 9 months and one year postoperatively. Patients' subjective preferences and radiological indices, including mechanical axis and coronal inclinations of the prostheses, were compared at one year postoperatively. NA-MIS TKA yielded better HSS and WOMAC total scores than CON TKA up to six months, and a better WOMAC pain score up to 9 months. However, these differences were not significant at one year postoperatively. ROM was comparable in both groups at all times, but more patients preferred the NA-MIS side to the CON side. Radiological results showed no differences in mean values between the two surgical groups, although the NA-MIS group contained fewer outliers than the CON group. In conclusion, NA-MIS TKA was associated with better clinical results up to 6 or 9 months after surgery, giving more accurate leg alignment than CON TKA.     

Recurrence of hepatitis B is associated with cumulative corticosteroid dose and chemotherapy against hepatocellular carcinoma recurrence after liver transplantation.

The incidence of hepatitis B (HB) recurrence after a liver transplantation has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine. However, the long-term incidence of recurrence is <10%, and the factors associated with HB recurrence are unclear. This study analyzed the factors associated with HB recurrence in 203 recipients who underwent liver transplantation for HB in 3 major centers in Korea over 4 years. Eighty-five patients (41.9%) had a hepatocellular carcinoma (HCC). Preoperative active virus replicators with the HBeAg(+) (46.8%) and/or hepatitis B virus DNA(+) (39.4%) were observed in 136 patients (67.0%). The HB prophylaxis consisted of either HBIG monotherapy (n = 95, HBIG group) or combination therapy with lamivudine (n = 108, combination group). HB recurrence was defined as the appearance of the HBsAg. The follow-up period was 28.3 +/- 13.1 months (mean +/- SD). HB recurred in 21 patients (10.3%) after transplantation. The time from transplantation to recurrence was 16.3 +/- 9.4 months. Pre-LT DNA positivity was more prevalent in HBIG group (55.8%) than in the combination group (39.8%) (P = 0.015). However, the incidence of HB recurrence was similar in the HBIG (6.3%) and combination group (13.8%), as well as between the active replicators (12.5%) and nonreplicators (4.1%) (P < 0.05). There was a far higher incidence of HB recurrence in patients receiving corticosteroid pulse therapy (21.0% vs. 7.9%), patients who experienced HCC recurrence (31.3% vs. 8.6%), and patients receiving chemotherapy to prevent HCC recurrence (25.0% vs. 4.4%) (P < 0.05). The cumulative corticosteroid dose was higher in patients who experienced recurrence of HB (P = 0.002). Multivariable analysis confirmed the effect of the cumulative corticosteroid dose and chemotherapy to be risk factors. Liver transplantation for HB is safe, with low recurrence rates if adequate prophylaxis is used. However, the cumulative corticosteroid dose and the chemotherapy used for HCC were risk factors for HB recurrence, so careful monitoring for HB recurrence is needed in these patients.     

Outcome of and prognostic factors for decompressive hemicraniectomy in malignant middle cerebral artery infarction.

Decompressive hemicraniectomy as an appropriate treatment for malignant middle cerebral artery (MCA) infarction is still a controversial issue. This study aimed to determine the survival rate and functional outcome, and factors associated with these, in patients with malignant MCA infarction. From January 2000 to December 2003, 60 patients with malignant MCA infarction were treated in our hospital. All patients in the study underwent a large ipsilateral craniectomy and duroplasty for decompression. The infarction territory was evaluated by either diffusion weighted magnetic resonance imaging or computed tomography. Clinical neurological presentation was evaluated using the Glasgow Coma Scale. Functional outcome was evaluated using the Barthel index (BI) and the Glasgow Outcome Scale (GOS) at follow-up 12 months later. Thirty-day mortality was 20% (12 patients) and 12-month mortality was 26.6%. The factors associated with higher mortality were age>or=60 years, involvement of more than one vascular territory, presence of signs indicating clinical herniation before surgery, and treatment more than 24 hours after ictus. The mean GOS score was 3.3+/-1.7. The mean Barthel index was 65.1+/-40.1. Twenty-nine (65.9%) patients had a favourable outcome (BI>or=60). The factors associated with favourable outcome were age<60 years and treatment within 24 hours of ictus, before clinical signs of herniation were noted. Decompressive hemicraniectomy should be performed in patients younger than 60 years within 24 hours of ictus before clinical signs of herniation develop. Age, timing of surgery and clinical signs of herniation are prognostic factors for mortality and functional outcome.     

15N nuclear magnetic resonance studies on the tautomerism of 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and other C8-substituted guanine nucleosides

The favored tautomeric and ionic structures were examined for the oxidative DNA damage adduct 8-hydroxy-2'-deoxyguanosine and its RNA analogue 8-hydroxyguanosine by 15N NMR spectroscopy. In addition, 15N chemical shifts and coupling constants from 13 different guanine nucleosides, including a wide variety of C8 substitutions (OH, SH, Br, OCH2C6H5, OCH3, SCH3, and SO2CH3), have been analyzed with respect to their tautomeric structures. A -98.5-Hz proton-nitrogen coupling constant observed for the N7 resonance of 8-hydroxyguanosine in dimethyl sulfoxide was evidence for 8-keto substitution, which is contrary to the structure implied by the generally used nomenclature. The pH dependence of 15N NMR spectra of 8-hydroxyguanosine in aqueous solution showed downfield shifts of the N1 and N7 resonances that were greater than 50 ppm, which indicated the conversion from a neutral 6,8-diketo to a 6-enolate-8-keto (pKa1 = 8.6) and finally to a 6,8-dienolate structure (pKa2 = 11.7). There was no evidence of an 8-enol substituent in the absence of ionization. It is proposed that the syn conformation of these oxidized bases in duplex DNA and RNA can be further stabilized by abnormal hydrogen bonding or mispairing that involves N7-H. The combined data show that 15N NMR is a sensitive probe to examine tautomerism of the guanine ring system. The analysis indicates that the change from a single to a double bond for the C8 substituent, and the accompanying removal of the normal double bond between N7 and C8 on the imidazole ring system, has no detectable effect on the tautomerism at the N1-O6 site of the pyrimidine ring system for both the 8-keto and 8-thio substitutions. In addition, large differences in electronegativity of the C8 substituents do not alter the N1-O6 tautomerism.     

123I-MIBG myocardial scintigraphy as a noninvasive screen for the diagnosis of coronary artery spasm

Background  It has been suggested that the sympathetic nervous system might play an important role in the development of coronary artery spasm. However, no cardiac imaging modality has been able to demonstrate abnormal sympathetic innervation in patients with coronary artery spasm. The purpose of this study was to assess the presence and location of abnormal sympathetic innervation using iodine 123-metaiodobenzylguanidine (¹²³I-MIBG) single photon emission computed tomography (SPECT) and to evaluate the clinical efficacy of ¹²³I-MIBG SPECT as a noninvasive screening test in patients with coronary artery spasm. Methods and Results  Coronary arteriography and a provocative test with intravenous administration of ergonovine maleate were performed in 26 patients (20 men, 6 women, mean age 48.2±12.0 years, range 20 to 67 years) who were suspected of having a coronary artery spasm. The subjects were divided into 2 groups: group 1 (n=18) comprised subjects with negative provocative provocative test result, and group 2 (n=8) comprised subjects with negative provocative test results. Ten healthy subjects served as controls. No abnormal MIBG uptake was observed in the control subjects. Abnormal sympathetic nervous innervation using ¹²³I-MIBG SPECT was observed either as a reduced uptake or a defective pattern in the perfused areas in 13 of the 18 regions supplied by vessels of ergonovine-induced vasospasm. Normal sympathetic innervation, as evidenced by normal ¹²³I-MIBG uptake, was noted in all of the 60 segments of normal vessel territories. Reduced uptake of ¹²³I-MIBG was not detected in the perfused areas of 5 vasospasm-induced vessels (perfusion territory of left anterior descending coronary artery [LAD] and the right coronary artery [RCA] in 2 and 3 patients, respectively). The sensitivity and specificity of ¹²³I-MIBG for detection of coronary artery spasm were 72.2% (95% confidence interval, [CI] 55% to 89%) and 100%, respectively. The positive predictive and negative predictive values were 100% and 92.3% (95% CI 91% to 93%), respectively. Conclusion   ¹²³I-MIBG SPECT is a feasible method to evaluate noninvasively and localize the territories of coronary arteries with spasm. Invasive diagnostic coronary arteriography with ergonovine provocation test may be unnecessary for diagnosis of coronary artery spasm in patients with typical resting pain, negative exercise test or normal thallium perfusion scan results, but showing abnormalities in ¹²³I-MIBG SPECT. Presented in part at the European Association of Nuclear Medicine Congress, September 1996, Copenhagen, Denmark.     

Hodgkin disease: contributions of chest CT in the initial staging evaluation

Chest radiographs and chest computed tomography (CT) scans were compared in 203 patients with newly diagnosed Hodgkin disease. The incidence of positive findings was tabulated from six intrathoracic lymph node groups, lung parenchyma, pericardium, pleura, and chest wall. The discordant cases were assessed to determine impact on clinical management. The CT scans provided additional evidence of disease involvement, ranging from 0% to 15% at each of the designated anatomic sites. Treatment was altered in 9.4% of all patients (19 of 203), including 13.8% (nine of 65) of those undergoing radiation therapy alone and 8.2% (ten of 122) of those undergoing combined-modality treatment. We conclude that routine chest CT examinations are valuable in the clinical management of those patients for whom radiation therapy is planned.